The miR-641-STIM1 and SATB1 axes play important roles in the regulation of the Th17/Treg balance in ITP

Sci Rep. 2024 May 16;14(1):11243. doi: 10.1038/s41598-024-61660-9.

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disease caused by T-cell dysfunction. Recently, several studies have shown that a disturbed Th17/Treg balance contributes to the development of ITP. MicroRNAs (miRNAs) are small noncoding RNA moleculesthat posttranscriptionally regulate gene expression. Emerging evidences have demonstrated that miRNAs play an important role in regulating the Th17/Treg balance. In the present study, we found that miR-641 was upregulated in ITP patients. In primary T cells, overexpression of miR-641 could cause downregulation of its target genes STIM1 and SATB1, thus inducing a Th17 (upregulated)/Treg (downregulated) imbalance. Inhibition of miR-641 by a miR-641 sponge in primary T cells of ITP patients or by antagomiR-641 in an ITP murine model could cause upregulation of STIM1 and SATB1, thus restoring Th17/Treg homeostasis. These results suggested that the miR-641-STIM/SATB1 axis plays an important role in regulating the Th17/Treg balance in ITP.

Keywords: Immune thrombocytopenia (ITP); SATB1; STIM1; Th17/Treg balance; microRNA 641 (miR-641).

MeSH terms

  • Adult
  • Animals
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Matrix Attachment Region Binding Proteins* / genetics
  • Matrix Attachment Region Binding Proteins* / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Purpura, Thrombocytopenic, Idiopathic* / genetics
  • Purpura, Thrombocytopenic, Idiopathic* / immunology
  • Purpura, Thrombocytopenic, Idiopathic* / metabolism
  • Stromal Interaction Molecule 1* / genetics
  • Stromal Interaction Molecule 1* / metabolism
  • T-Lymphocytes, Regulatory* / immunology
  • T-Lymphocytes, Regulatory* / metabolism
  • Th17 Cells* / immunology
  • Th17 Cells* / metabolism

Substances

  • Matrix Attachment Region Binding Proteins
  • MicroRNAs
  • Neoplasm Proteins
  • SATB1 protein, human
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • MIRN641 microRNA, human